Systems, models, and methods for simulating surgery on anatomical organs

ABSTRACT

The invention provides systems and methods for improved simulation of surgical procedures, using models of anatomical organs. The models comprise models of internal components present in the anatomical organ. The models of the internal components are registered to the position which the internal component occupies in the anatomical organ, and in some embodiments the models of the anatomical organ can lose simulated physiological fluids during simulated surgery.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.15/299,435, filed Oct. 20, 2016, which claims the benefit of U.S.Provisional Application No. 62/244,410, filed Oct. 21, 2015; thecontents of both applications are incorporated herein by reference

STATEMENT OF FEDERAL FUNDING

Not applicable.

BACKGROUND OF THE INVENTION

Considerable effort has been expended in recent years to improvesurgical training for medical students and to allow experienced surgeonsto practice approaches before tackling difficult cases. Surgery onanimals can give practitioners the feel of tissues and organs, but doesnot provide an adequate simulation human anatomical structures anddimensions, while surgery on cadavers, which have typically beenembalmed, does not provide the “feel” of surgery on living tissues.

One approach to improving surgical training has been the development ofsurgical models of human organs which can reproduce the anatomy anddimensions of the organs, as aids to simulate the surgical experience.Recently, surgical models have been provided using hydrogels which havebeen shaped to simulate an organ of choice. U.S. Pat. No. 8,870,576, toMillon et al. (“Millon”), discloses surgical aids formed from hydrogels,which the patent states exhibit some mechanical properties (such as“feel”) of organs. Millon further discloses forming a tubular structurewithin a hydrogel by placing a rod within the hydrogel and thenwithdrawing it.

There remains in the art a need for better means for simulating thesurgical experience, not only for training medical students and surgicalresidents, but also for training even experienced surgeons oncomplicated surgeries and for practicing or developing ways to ofapproach unusual or difficult surgical problems. It would also beadvantageous if there was a better means for medical devicemanufacturers to develop, test and demonstrate use of devices to assistin performing surgery and for filmmakers and others to simulate surgery.Surprisingly, the inventive systems, models, and methods fulfill theseand other needs.

PARTIES TO JOINT RESEARCH AGREEMENT

Not applicable.

REFERENCE TO SEQUENCE LISTING OR TABLE SUBMITTED ON COMPACT DISC ANDINCORPORATION-BY-REFERENCE OF THE MATERIAL [SPECIFY NUMBER OF DISCS ANDFILES ON EACH]

Not applicable.

SUMMARY OF THE INVENTION

In some embodiments, the invention provides systems for simulatingsurgery on an anatomical organ. In these embodiments, the systemscomprise a model of the anatomical organ, the model composed of acrosslinked hydrogel simulating a tactile property of the anatomicalorgan, and having disposed in the model at least one internal structureor internal void having a size, shape and position within said modelmapped to an internal structure or void having a like, shape andposition within the anatomical organ. In some embodiments, the systemsfurther comprise a plurality of internal structures or internal voids.In some embodiments, the internal structure or internal void is notlinear within the model for more than two contiguous inches. In someembodiments, the internal void is a channel in the hydrogel. In someembodiments, the at least one internal structure is a simulated arteryor vein of the anatomical organ. In some embodiments, the simulatedartery or vein contains simulated blood. In some embodiments, at leastone internal structure or internal void in the model contains asimulated physiological fluid of the anatomical organ. In someembodiments, the simulated physiological fluid is simulated blood. Insome embodiments, the anatomical organ being modeled is a kidney orbladder and the simulated physiological fluid is urine. In someembodiments, the anatomical organ being modeled is a brain and thesimulated physiological fluid is cerebrospinal fluid. In someembodiments, the anatomical organ is a gall bladder and the simulatedphysiological fluid is bile. In some embodiments, the system furthercomprises at least one simulated tumor disposed in or on said model ofsaid anatomical organ. In some embodiments, the tumor is at a positioncorresponding to a position at which tumors occur in the anatomicalorgan. In some embodiments, the model contains a plurality of simulatedtumors at positions corresponding to positions at which tumors occur inthe anatomical organ.

In another group of other embodiments, the invention provides models ofan anatomical organ of interest, comprising: a crosslinked hydrogelhaving the physical shape and size of the organ of interest, whichhydrogel simulates a tactile property of the anatomical organ, andhaving disposed in the model at least one internal structure or internalvoid having a size, shape and position within the model, which size,shape and position are mapped to a corresponding internal structure orvoid having a like, shape and position within the anatomical organ ofinterest. In some embodiments, the model comprises a plurality ofinternal structures, internal voids, or both. In some embodiments, theinternal structure or internal void within the model is not linearwithin the model for more than five mm. In some embodiments, theinternal void is a channel in the hydrogel. In some embodiments, thechannel is a simulated artery or vein of said anatomical organ. In someembodiments, the simulated artery or vein contains simulated blood. Insome embodiments, the model is connected to a fluid bag external to themodel to create a pressure on the simulated blood within the simulatedartery or vein. In some embodiments, the pressure on the simulated bloodwithin the simulated artery model is pulsatile. In some embodiments, theat least one internal structure or internal void contains a simulatedphysiological fluid of the anatomical organ. In some embodiments, thesimulated physiological fluid is simulated blood. In some embodiments,the anatomical organ of interest is a kidney or bladder and thesimulated physiological fluid is urine. In some embodiments, theanatomical organ of interest is a brain and the simulated physiologicalfluid is cerebrospinal fluid. In some embodiments, the anatomical organof interest is a gall bladder and the simulated physiological fluid isbile. In some embodiments, the model comprises at least one simulatedtumor. In some embodiments, the simulated tumor is at a positioncorresponding to a position at which tumors occur in the anatomicalorgan of interest. In some embodiments, the model comprises a pluralityof simulated tumors at positions corresponding to positions at whichtumors occur in the anatomical organ. In some embodiments, one or moremodels of organs are covered with one or more layers of additionaltissue, such as fascia, fat or muscle or a combination thereof, that inthe body would be encountered in the course of operating on the organ ofinterest. In some embodiments, to provide a better simulation of surgeryon the organ of interest as it is found in the body, the model of theorgan is disposed in a model of the abdomen or of the torso, with modelsof other organs disposed around the organ of interest in theconfiguration in which they are found in the body.

In a further group of embodiments, the invention provides methods forsimulating surgery on an anatomical organ of interest. These methodscomprise providing a crosslinked hydrogel model having a shape and sizecorresponding to a shape and size of the said anatomical organ ofinterest, which hydrogel simulates a tactile property of the anatomicalorgan, and having disposed in the model at least one internal structureor internal void having a size, shape and position within the model,which size, shape and position are mapped to a corresponding internalstructure or void having a like, shape and position within theanatomical organ, and allowing simulated surgery to be conducted on saidmodel, thereby simulating surgery on the anatomical organ of interest.In some embodiments, the model comprises at least one channelcorresponding to least one artery or vein in the anatomical organ, thechannel containing a first simulated physiological fluid. In someembodiments, the method further comprises the step of collecting any ofthe first simulated physiological fluid released from the model duringthe simulated surgery. In some embodiments, the method further comprisesmeasuring the collected first simulated physiological fluid releasedduring the simulated surgery to obtain a first measurement of loss ofthe first simulated physiological fluid during the simulated surgery. Insome embodiments, the method further comprises determining an average ofloss of the first simulated physiological fluid during simulated surgeryon a like model of the anatomical organ by a group selected from thegroup consisting of (i) medical students, (ii) surgical residents, and(iii) surgeons with a board certification encompassing surgery on theanatomical organ, and comparing the first measurement of loss of thefirst simulated physiological fluid during said simulated surgeryagainst the average of the first simulated physiological fluid lostduring simulated surgery by of any of groups (i), (ii) or (iii). In someembodiments, the model of the anatomical organ of interest comprises asecond physiological fluid, which second physiological fluid occurs inthe anatomical organ of interest either normally or in a pathologiccondition of interest. In some embodiments, the second physiologicalfluid is disposed within the model in an internal structure or voidcorresponding to where the second physiological fluid occurs in theanatomical organ of interest. In some embodiments, the method furthercomprises the step of collecting any of the second simulatedphysiological fluid released from the model during the simulatedsurgery. In some embodiments, the method further comprises measuring thecollected second simulated physiological fluid released during saidsimulated surgery to obtain a first measurement of loss of the secondsimulated physiological fluid during the simulated surgery. In someembodiments, the method further comprises determining an average of lossof the second simulated physiological fluid during simulated surgery ona like model of the anatomical organ by a group selected from the groupconsisting of (i) medical students, (ii) surgical residents, and (iii)surgeons with a board certification encompassing surgery on saidanatomical organ, and comparing said first measurement of loss of saidsecond simulated physiological fluid during said simulated surgeryagainst said average of any of groups (i), (ii) or (iii). In someembodiments, the method further comprises collecting all simulatedfluids released during simulated surgery on the model of the anatomicalorgan. In some embodiments, the fluids may be collected separately,while in other embodiments, they may be collected together. In someembodiments, the method further comprises measuring the collected allsimulated fluids released during the said simulated surgery to obtain afirst measurement of loss of all of the simulated fluids during thesimulated surgery. In some embodiments, the method further comprisesdetermining an average of loss of the second simulated physiologicalfluid during simulated surgery on a like model of the anatomical organby a group selected from the group consisting of (i) medical students,(ii) surgical residents, and (iii) surgeons with a board certificationencompassing surgery on the anatomical organ, and comparing the firstmeasurement of loss of said the simulated physiological fluid duringsaid simulated surgery against the average of any of groups (i), (ii) or(iii). In some embodiments, the method further comprises.

In some embodiments, the invention provides methods for comparingperformance by a first practitioner in a simulated surgery on a model ofan anatomical organ to the performance of a second practitioner onsimulated surgery on a model of the same anatomical organ, the methodcomprising: (a) providing a first model of the anatomical organ, thefirst model composed of a crosslinked hydrogel simulating a tactileproperty of the anatomical organ, and having disposed in the model atleast one internal structure or internal void having a size, shape andposition within the model mapped to a corresponding internal structureor void having a like, shape and position within the anatomical organ,wherein the at least internal structure or internal void contains aspecified simulated physiological fluid of the anatomical organ, (b)having the first practitioner perform a specified simulated surgery onthe anatomical organ, (c) collecting the specified simulatedphysiological fluid released during the simulated surgery to obtain afirst measurement of the amount of the simulated physiological fluidlost during the simulated surgery by the first practitioner, and (d)comparing the first measurement of the specified simulated physiologicalfluid lost during the simulated surgery against a second measurement,which second measurement is of the specified physiological fluid lost ina like specified simulated surgery on a like second model of theanatomical organ by the second practitioner, wherein a loss of less ofthe specified physiological fluid during the simulated surgery by thefirst practitioner indicates that the first practitioner performs aswell or better than the second practitioner and a loss of more of thespecified physiological fluid indicates that the first practitionerperforms worse than the second practitioner, thereby comparing theperformance by the first practitioner in performing said simulatedsurgery to that of the second practitioner. In some embodiments, thesimulated physiological fluid is simulated blood. In some embodiments,the second practitioner is (i) a medical student, (ii) a surgicalresident, or (iii) a surgeon with a board certification encompassingsurgery on the anatomical organ. In some embodiments, the methodcomprises collecting a first total of all simulated physiological fluidsreleased during the simulated surgery on the first model of theanatomical organ and a second total of all simulated physiologicalfluids released during the simulated surgery on the like second model ofthe anatomical organ and comparing the first total to the second total.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 . FIG. 1 is a photograph showing an early embodiment in which awhite block 101 has had a cavity 102 formed within it to provide a moldof half of a kidney. When later filled with hydrogel, the negative space102 will create a model having the exterior geometry of the kidney.

FIGS. 2A and B. FIGS. 2A and 2B are photographs of an exemplar pair of3D printed molds of the interior geometry (FIG. 2A) and exteriorgeometry (FIG. 2B) of half of a longitudinal section of calyxes, renalpelvis and ureter.

FIG. 3 . FIG. 3 shows a model of an idealized kidney with 3 tumors and acalyx system that can hold simulated urine.

FIG. 4 . FIG. 4 is a photograph of a portion of a surgery to resect asimulated tumor from a model of a kidney, using a da Vinci® surgicalsystem. Simulated blood from a simulated blood vessel feeding the tumoris visible around the surgical device.

FIG. 5 . FIG. 5 is a schematic diagram showing aspects of mappinginternal structures or features of a model organ by using “suspensioncables” such as wires or filaments to position the internal structuresor feature so that they appear in the correct anatomical position in themodel (or, for structures intended to appear in a position found only ina pathological condition, in the anatomical position found in thepathological condition.)

DETAILED DESCRIPTION

Training surgeons to perform surgery on organs, and particularly onanatomical features specific to pathological conditions, is important toimproving patient outcomes and reducing healthcare costs. In initialstudies underlying the work disclosed herein, the inventors hadvolunteer practitioners of three different levels of expertise, medicalstudents, surgical residents, and board certified surgeons, performsimulated surgery on hydrogel models of an exemplar anatomical organ todetermine how well surgery on such models recreated the experience ofoperating on the anatomical organ itself. The time spent by each of thevolunteers in performing the surgery was recorded.

The inventors found that, for each level of expertise, the duration ofsurgery by the volunteers on the hydrogel models of the exemplaranatomical organ was markedly shorter than the duration of surgery onthe actual anatomical organ, suggesting that surgery on the hydrogelmodels failed to recreate the experience of surgery on the actualanatomical organ. To understand this, the inventors interviewed thepractitioners. The practitioners indicated that, although the hydrogelmodels felt and looked like the anatomical organ, the models failed toengage the practitioners' interest, and so the practitioners movedthrough the simulated surgery without exercising the care and precisionthey would have exercised in actual surgery. Further inquiry revealedthis lack of engagement was because the models did not bleed. Morespecifically, the model organs did not provide feedback by showing thebleeding consequent to cutting major vessels in the anatomical locationsin which they would be found in the anatomical organ. Without thisvisual feedback, there was no drawback during the simulated surgery tocutting a blood vessel the practitioner would normally take care toavoid during actual surgery. Moreover, without a sense of overall bloodloss during the simulated surgery, the practitioner did not have a senseof urgency, whereas in actual surgery, reducing the duration of thesurgery while minimizing overall blood loss are important, butcompeting, metrics of the surgeon's performance. The inventors concludedthat surgery on organ models that do not simulate loss of blood frommajor vessels (and by extension, other fluids found in any particularorgan being operated on) is of limited value in creating an experiencethat simulates actual surgery.

Surprisingly, the inventors have solved some of the problems notaddressed by previous physical and hydrogel models. The inventivesystems, models, and methods provide feedback to the practitioner andprovide a more accurate simulation of surgery than previously availablesurgical systems and models. Furthermore the inventors found that themetrics of performance measured using the inventive systems, models andmethods correlated to the same metrics of performance in human surgery.Therefore, use of the inventive systems, models and methods are believedto allow the practitioner to compare the metrics of his or herperformance to the same metrics of performance of other practitioners atthe same level of experience, or at greater or lesser levels ofexperience. Moreover, the inventive systems, methods and models allowprofessors, preceptors, and certification groups to compare performanceparameters for a practitioner's surgery on the inventive models toaverages of practitioners on the inventive models to determine the levelof skill attained by the practitioner at the time the simulated surgerywas performed and to predict future performance in surgery on patients.And, the systems, models and methods provide improved ability to test ordemonstrate surgical robots or other aids to performing surgery, or tosimulate surgery for cinematographic or other uses.

The inventive systems, models, and methods allow for simulating internalstructures or pathology in the organ model, such as tumors that involvea portion of the organ or vascular malformations, with the internalstructures or pathology registered to be in the correct anatomicposition. Further, in some embodiments, they allow full proceduralsimulation using fluids that mimic physiological fluids relevant to theorgan of interest, such as simulated blood that can leak from incisionsin the organ model. In some embodiments, the systems and methods allowfor simulated blood vessels to be connected to an external fluid sourcecreating a pressure in simulated blood vessels and, in some embodiments,to be connected to a device that provides pulses of pressure to simulatethe natural pulse of blood in the organ being modeled.

OVERVIEW

This section provides an overview of aspects of the inventive systemsand methods and models. Aspects that need more detailed discussion arethen addressed in succeeding sections.

The inventive systems and models can be made for most if not all organs.For ease of reference, the particular organ being modeled for simulatedsurgery will generally be referred to herein by one of the followingterms: the “target organ”, the “subject organ”, or the “organ ofinterest”.

A model of an organ of interest is preferably made with the exteriorgeometry (or “outside geometry”) of that organ. The making of molds foruse in crafts, art and sculpture, is well known, and many techniquestraditionally used in making such molds, such as casting or carving, canbe used or readily adapted for making molds useful in the inventivesystems and models. It is assumed that persons of skill are familiarwith these techniques, but a brief description will be presented here asbackground for methods for making the models used in some embodiments ofthe invention.

As persons familiar with modeling and casting are aware, molds havehollow cavities with an interior surface. When casting material isflowed into the hollow cavity and solidified, the resulting “piece” or“casting” has an exterior shaped by the interior surface of the mold.The shape of the casting produced by solidifying material in a mold maytherefore be thought of as the positive shape of the negative shapeformed by the interior surface of the mold. The interior surfaces ofmolds used in the inventive systems and methods are therefore designedto be negative spaces which, when casting material is flowed into them,will result in castings which reproduce the exterior surface, size andshape of the organ of interest or of a selected structure within theorgan. (As discussed further within, selected structures are typicallycast so that they may be later positioned within a model of the organ.)

Molds used to form organ models for use in the inventive systems andmethods can be made by any of a number of conventional methods. It isassumed that persons of skill are familiar with these conventionalmethods, but two will be mentioned as examples. One method that can beused is so-called “bi valve molding,” which uses two molds. Typically,the two molds are longitudinal sections and are usually sagittalsections. To obtain such sections, a “parting line” is drawn along theexact middle of the object to be modeled, the molds of each half aremade, and the molds are registered to each other so that when the twomolds are joined together, or the casts from each mold are joinedtogether to assemble the model, they will align perfectly. A secondexample is “piece-molding,” which uses more than two molds, each ofwhich relates to a different contiguous portion of the object and whichtogether are assembled to form a model of the entirety of the object.For convenience, the discussion below will generally be phrased with theassumption that two molds are used and that the molds are symmetricalhalves. It will be understood, however, that unless otherwise requiredby logic or context, more than two molds could be used to togetherprovide pieces that together will constitute the entirety of the organof interest being modeled. It will also be noted that, for convenienceof reference, it will be assumed that the two molds being used aresymmetrical halves of the organ being molded, but that in many cases themolds can be of any two complementary proportions adding up to 100% ofthe organ that the moldmaker finds convenient. As the anatomical organsmodeled in the inventive systems, models and methods typically haveinternal structures and voids that require placement and removal ofvarious elements, and given the constraints of having hydrogelcrosslinked around such internal structures or voids, when using twomolds, their complementary proportions will typically be within about10% of 50%, such as 45%/55% or 40%/60%, with “about” here meaning 2%plus or minus of the stated percentage. Proportions that do not allowdesired internal structures or voids to be registered in the molds toresult in having the desired anatomical feature in a position within themodel of the organ of interest corresponding to that of the natural orpathological internal structure or void can be readily determined by thepractitioner and are not preferred.

In some embodiments, molds can be made by placing a blanket of siliconeor mold rubber around an organ from a cadaver and then forming ahardshell, or “mother” mold over the silicone or mold rubber, from whichone or more castings can then be made. In some embodiments, the mold canbe made using 3D printing. Three dimensional printing not only isconvenient, but also makes it relatively easy to create models ofpathology, such as exophytic or endophytic tumors or vascularabnormalities, which can useful in training surgeons in difficult orless common surgical problems. Some embodiments of the inventive systemsand methods contemplate that the model of the subject organ comprisesinternal voids, structures, or both, which are present in the subjectorgan. In some embodiments, this is accomplished by first forming moldsof halves of the exterior of the organ, using the molds to form hollowmodels of each half, each of which has the internal and externalgeometries of the relevant half of the organ, placing components tomimic the internal voids or structures in the respective halves, flowinghydrogel into the portion of the hollow of each half that remains aroundthe components, and then joining the two halves together to form a modelof the intact organ.

In some embodiments, we have found it convenient to create models ofinternal voids by freezing ice in the desired shape of the internalvoid, such as a half of a brain ventricle, and then using the shaped iceas the “positive” mold within the negative mold of, for example, a halfof a brain. The positive shaped ice is registered within the negativemold of the organ half being modeled so that when the organ model iscomplete, the internal feature (such as the ventricle being discussed asan example) will be in the desired physical position within the organmodel. Hydrogel is then introduced into the negative mold but can not,of course, flow into the space filled by the ice. The hydrogel is thencrosslinked. Where the crosslinking is by the preferred method offreeze/thawing, the ice will melt during the thaw portion, and the meltwater will drain out, leaving the desired void. Since use of an icepositive mold allows only a single freeze/thaw cycle, the concentrationof the polymer, such as PVA, is typically increased so that theresulting model of the organ being modeled is of a stiffnesscorresponding to that of the anatomical organ being modeled. It isroutine for persons of skill in the art of making hydrogel models to usedifferent combinations of polymer concentrations and numbers offreeze/thaw cycles to result in hydrogel models of particularstiffnesses. Since only one freeze/thaw cycle is used when ice molds areused to model voids in an organ, the practitioner wishing to use ice asa positive mold to model a void in any particular organ to be modeledneed only fill some molds with different concentrations of hydrogel, runthem through one freeze/thaw cycle, and have them felt by a practitionerfamiliar with the “feel” of the organ in question to select the one withthe stiffness of the organ being modeled. If the stiffness of thecrosslinked polymers produced by the particular concentrations used isnot quite right, a further set of molds can be filled with polymer atconcentrations suggested by the results of the first series to arrive atone producing the stiffness (the “feel”) of the organ being modeled.

FIG. 1 depicts an early embodiment in which a white block 101 has had acavity 102 formed within it to provide a mold of half of a kidney. Whenlater filled with hydrogel, the negative space 102 will create a modelhaving the exterior geometry of the kidney. The lower portion of themold 102 shown in FIG. 1 further comprises a hollow area 103 in theblock exterior corresponding to the external geometry of a structurewhich, when the mold 102 is filled with hydrogel, will model the renalpelvis and ureter. FIG. 1 also shows a ball 104 which mimics a tumorprotruding from the organ. Although not visible in this Figure, theportion of the block behind the ball 104 has a negative space to acceptthe ball. In some later embodiments, the molds are designed toincorporate models of tumors at positions which present either common ordifficult surgical problems, depending on the intended training orpractice purpose for the resulting surgical model.

As can also be seen in FIG. 1 , elements can be disposed in the hollowinterior of the mold 102 of this half of the organ to create models ofvoids or internal structures in the organ. The elements are preferablymapped or registered to the corresponding locations of the voids orinternal structures in the organ being modeled. In FIG. 1 , theseelements are pliant wires 105 which are disposed to represent the renalartery and vein, as well as a blood supply 106 for the “tumor” 104. (Inthe example shown in FIG. 1 , the wires 105 and 106 enter the mold forthe kidney through the area 103.) To complete the model of this half ofthe kidney, a mix containing hydrogel monomers is allowed to flow intothe negative space 102 and the monomers are crosslinked to form ahydrogel polymer of a first desired stiffness, the wires 105 and 106 aregently pulled out, leaving behind void spaces in the hydrogel. In someembodiments the hydrogel polymer is then firmed to a second desiredstiffness. For example, if the crosslinking is performed by subjectingthe hydrogel to freeze/thaw cycles, the hydrogel monomers may besubjected to a first freeze/thaw cycle, the wires (or any other elementsto be removed) removed, and the hydrogel subjected to furtherfreeze/thaw cycles to bring the stiffness up to the stiffness of thesubject organ. Alternatively, in some embodiments, the wires or otherelements are removed after the crosslinking is completed, but before theassembly of the organ model is completed. In some embodiments, ratherthan wires 105 and 106, the elements can be filaments of a materialwhich is dissolvable by a solvent that will not dissolve crosslinkedhydrogel or which will dissolve the filaments much more quickly than itwill the crosslinked hydrogel, allowing the filaments to be dissolvedand the solvent removed before too much of the hydrogel is dissolved toaffect the utility of the model organ. For example, suppliers such asMaker Bot Industries, Inc. (Brooklyn, NY), sell high impact polystyrene,or “HIPS,” as a dissolvable filament for use in 3D printing. HIPS andother styrene filaments are dissolvable in limonene (preferably(R)-(+)-limonene, rather than the more common D-limonene). Once hydrogelhas been flowed into the mold and crosslinked to a first desired degreeof stiffness, the solvent can then be used to dissolve the filaments,leaving the desired channels or voids.

In other embodiments, internal voids and structures can be modeled bycreating separate one piece or multiple piece hollow molds for theinternal void or structure. FIGS. 2A and B show an exemplar pair of 3Dprinted molds 201 and 202, of the interior geometry 201 and exteriorgeometry 202 of half of a longitudinal section of calyxes, renal pelvisand ureter. The interior mold 201 and exterior mold 202 are registeredso that when they are mated together and hydrogel is flowed into theresulting combined mold and then crosslinked, the combined mold willcreate a positive hydrogel model of half of a longitudinal section ofcalyxes, renal pelvis and ureter. Visible at the edges of FIGS. 2A and2B are projections 203 and depressions 204 in the molds, which can onlybe mated when molds 201 and 202 are aligned in the correct orientation.Two of these hydrogel models can then be mated and attached to oneanother to form a model of the intact calyxes, renal pelvis and ureter.The resulting model of the calyxes can be registered within the cavityof a mold of the kidney. The remaining space within the cavity is thenfilled with hydrogel, and crosslinked to the degree of stiffness desiredby the practitioner, which will usually be a stiffness mimicking that ofthe organ being modeled.

FIG. 3 shows a model 301 of an idealized kidney with 3 tumors 302 and acalyx system 303 that can hold simulated urine. The tumors 302 areplaced at distances from the calyx to produce differing degrees ofdifficulty from calyx breach during surgery on the model 301.

In models of the brain, surgical challenges can be simulated byincorporating into the overall model separate models of one or moreinternal structures such as the ventricles, amydala, hippocampus,pituitary gland, thalamus, hypothalamus, cerebellum and brainstem. Thesestructures are typically separately molded as wholes or halves andregistered into molds of the appropriate halves of the brain so thatwhen the overall model is created, the internal structures are in thecorrect anatomical position.

A similar process using two molds can be used to form simulated bloodvessels having a lumen. In some embodiments, the simulated vessel ispositioned in the hollow shell of the organ's exterior geometry or, insome embodiments, is placed within the mold of the organ's exteriorgeometry. The simulated blood vessel is then mapped within the mold ofthe organ to the internal positions in the organ of the correspondingblood vessel within the organ. In some embodiments, the simulated bloodvessel has a distal end that extends beyond the exterior of the organmodel. This distal end can be cannulated and attached, typically throughtubing, to a fluid bag containing simulated blood, as described furtherbelow. Further, pliant wires or other pliable but positionable materialscan be placed running from the distal (outside the organ) end, throughthe lumen, and out the proximal end within the organ, with the portionsemerging from the proximal end positioned to simulate the path ofsmaller blood vessels connected to the larger simulated blood vesselthrough which the wires or other materials run. Hydrogel is then flowedinto the cavity of the mold of the organ. After the hydrogel iscrosslinked to the desired degree of stiffness, the wires or othermaterial can be gently withdrawn through the lumen of the simulatedblood vessel, leaving behind voids in the hydrogel simulating smallerblood vessels.

As noted, the distal end of the simulated blood vessel can be connectedto a fluid bag or other container holding simulated blood. The bag orcontainer can be suspended to provide a simulation of blood pressure tothe simulated blood. In some embodiments in which the simulated bloodvessel is intended to simulate an artery, such as the renal artery, theextended distal end is attached to tubing connected directly orindirectly to a pump or other device which creates pulses of pressure inthe simulated blood, thereby creating a simulation of arterial pulsingin the simulated artery in the organ model. Alternatively, if thesimulated blood is in a fluid bag or other flexible container, the bagor other container can simply be rhythmically gently squeezed throughouta simulated surgery to simulate a pulse. FIG. 4 is a photograph showinga portion of a simulated surgery on kidney model 401 in which anexophytic tumor 402 is being resected using a da Vinci® surgical system403 (Intuitive Surgical, Inc., Sunnyvale, CA). Simulated blood 404 froma simulated blood vessel feeding the tumor 402 is visible around the daVinci surgical system 403.

The use of simulated blood, other physiological fluids relevant to thesimulated organ, or both, not only increases the accuracy of thesimulation but also engages the practitioner's attention, unlike surgeryon simulated organs that do not show simulate bleeding, which were shownin the studies noted above not to engage the practitioner's attention.In some embodiments, the time taken by a practitioner to perform aparticular simulated surgery on the simulated organ (for example, toremove one or more simulated tumors or vascular abnormalities) is timed.For evaluation purposes, the simulated organ operated on by thepractitioner can also be examined to determine whether the simulatedsurgery successfully removed the pathology modeled into the organ(surgeries are not typically performed on normal organs) and theprecision and accuracy of the incisions, closing and other technicalaspects. The time can then be compared to the average times known in theart to be taken by practitioners of different levels of experience orexpertise in similar surgeries to determine whether the practitionerperformed at the level expected for someone with the practitioner'slevel of experience, exceeded it, or was below it.

In some embodiments, simulated blood released during the simulatedsurgery is measured to determine “blood loss.” The “blood loss” can bedetermined by any of a number of means, such as by collecting the“blood” in a container positioned under the model and then measuring theaccumulated “blood,” or by measuring or using a known amount of “blood”in the simulated blood vessels at the beginning of the simulated surgeryand determining the amount remaining at the end. It is anticipated thatsimulated blood will be used in all simulated surgeries. A number oforgans, however, also contain an additional physiological fluid, such asurine, cerebrospinal fluid, or bile. If the organ whose surgery is to besimulated normally has such an additional physiological fluid present,this fluid can also be simulated by a fluid (such fluids are sometimesreferred to herein as “simulants”), which will typically be colored tomatch the color of the physiological fluid. If physiological fluid has adifferent color or clarity when a certain pathological condition is arepresent and the model is intended to simulate surgery on an organ withthat condition, the simulant can be colored to be similar to the colorof the physiological fluid and agents, such as flour or powdered chalkcan be added to reduce the clarity to the cloudiness present in thepathologica condition.

The release of the simulant during the simulated surgery is preferablymeasured. The amount of simulant released can then be used to comparethe practitioner's performance in the same manner as that discussedregarding the amount of simulated blood released. Persons of skill willappreciate that when loss of both blood and a second physiological fluidare to be measured, one can either measure total fluid loss by capturingfluids released during the simulated surgery in a container, or bystarting with known amounts of each fluid and then determining theamount of each left at the end of the simulated surgery.

As with the comparison of times discussed above, the amount of simulatedblood released, or of a simulant of a second physiological fluid, orboth, can be compared to the average amount of blood, physiologicalfluid, or both, known or determined to be released by practitioners ofdifferent levels of experience or expertise in similar surgeries todetermine whether the practitioner performed at the level expected forsomeone with the practitioner's level of experience, exceeded it, or wasbelow it. For operations in which the average amount of loss of blood,of a second physiological fluid, or both, is not known, a database canreadily be constructed by, for example, having a number of practitionersfrom groups such as medical students, surgical residents and boardcertified surgeons perform simulated surgery on models with definedpathologies, and determining the average loss of fluid or fluids insurgeries by practitioners in each group, which can then be used as abase of comparison for loss of fluid or fluids by practitioners in latersimulated surgeries on similar models.

The description above explains systems and methods using models of asingle organ. Persons of skill will recognize that models can be made ofmultiple organs, with the organs disposed in a simulated abdomen ortorso to provide a simulation of the organs in their native threedimensional presentation in the body, and comprising one or more layersof hydrogel positioned to simulate connective tissue, fat, and muscle.Such simulated abdomens and torsos provide systems and methods with yetimproved simulations of the surgical experience.

Definitions

As used herein, the term “organ” refers to an organ of a mammal. In someembodiments, the organ may be an organ of an animal, such as a cow, pigsheep, dog or cat. In some preferred embodiments, the organ is a humanorgan.

As used herein, the phrases “organ of interest” and “anatomical organ ofinterest” are used interchangeably and denote a particular organ whichhas been selected by the practitioner to practice surgery on that organ.

A “model” of an organ of interest is a crosslinked hydrogel model thatis designed to have an intended size and shape of the organ of interestand which, as described below, is crosslinked to have a feel as similaras possible to that of the organ being modeled. The size of the organwill be smaller or larger, depending on whether it is intended tosimulate an organ from a pediatric or an adult patient, and its shapemay be varied to provide a model of, for example, an organ that has hadprevious surgery and now presents a challenging surgical problem.

As surgeons, pathologists, anatomists, and other persons who havehandled fresh organs will appreciate, the various organs and tissues inthe body have characteristic stiffness or softness due to, among otherthings, a combination of internal structure, the presence or absence ofconnective tissue, and the composition of their tissues, all of whichresults in the organ having a characteristic “feel.” For example, fattends to be soft, while muscle is somewhat stiffer. Brains have asoftness similar to gelatin, while kidneys are firm. Pathology may alsohave a characteristic feel. For example, a tumor in an organ may feelsofter or harder than the parenchyma or connective tissue normallypresent in that organ and the presence of the tumor may be detected by asurgeon who extends his or her fingers into an incision and feels thetumor's firmness. The inventive models of organs of interest and ofpathology (such as tumors) within organs of interest are intended inpart to simulate the stiffness or softness—the “feel”—of the organ orpathology being modeled. This “feel” is sometimes referred to herein asthe “tactile property” of the anatomical organ or pathology.

As used herein, the phrase “physiological fluid” refers to a fluid thatis normally present in a particular organ of interest, or which is foundin that organ in a particular pathological condition. A “simulatedphysiologic fluid” is a fluid that simulates a physiologic fluid. Forexample, blood is a physiological fluid present within arteries, veins,or both within most if not all organs and may be simulated by watercolored with a red food dye (particularly to simulate arterial blood) ora blue food dye (to simulate venous blood).

As used herein, the terms “mapped” or “registered” in relation to aninternal structure or void in a model of an anatomical organ mean thatthe model of the organ (a) has a model of an internal structure or voidoccurring in the anatomical organ, either normally or in a pathologicalcondition, and (b) that the model of the internal structure or void ispositioned within the model of the organ at a location corresponding tothe position of the internal structure or void of the organ beingmodeled.

In some embodiments, models according to some embodiments of theinvention are used to test or to demonstrate the proficiency of a personby comparing the loss of one or more fluids during simulated surgery bythat person to the average loss of the same fluid or fluid duringsimulated surgery on a like model by a group of practitioners selectedfrom (i) medical students, (ii) surgical residents and (iii) surgeonsboard certified for surgery on the organ of interest (for example,neurosurgeons for simulated surgery on a model of the brain, orurologists for simulated surgery on a model of a bladder). As usedherein, the phrase “simulated surgery on a like model of the anatomicalorgan” means that the model on which simulated surgery is performed bythe person whose proficiency is being tested or demonstrated and themodels being subjected to simulated surgery by the medical students,surgical residents, or board certified surgeons are of the same size andshape, are of hydrogel crosslinked to the same degree of stiffness (forexample, by having the same polymer mix and concentration and havingbeen subjected to the same number of freeze/thaw cycles), have the samemodeled internal structures, voids, or both, have the same simulatedphysiological fluid or fluids disposed in the same way in the samepositions and, if one of the fluids is under pressure, the pressure isthe same in the model being used by the person whose proficiency isbeing tested or demonstrated and the models being subjected to simulatedsurgery by the medical students, surgical residents, or board certifiedsurgeons.

Organs and Blood Vessels

It is contemplated that the inventive systems and methods can be used tomodel virtually any organ. In addition to the kidney, which was used asan exemplar organ in the studies underlying the present disclosure,other organs which can conveniently be modeled include the bladder, gallbladder, liver, pancreas, uterus, ovaries, heart, lungs, spleen, bowel,and brain. In some embodiments, the organ which can be modeled is an eyeball.

Over the past century, every organ in the body has in the aggregate beenoperated on hundreds of thousands of times. The range of sizes of eachorgan both in adults and in children of different ages is therefore wellknown, as are unusual sizes which certain organs may have due to naturalvariations or pathology. The liver, for example, may undergo enlargementin a number of conditions, such as infection or a metabolic disorder. Itis expected that molds can be created to model organs of different sizesdepending on the age of the hypothetical patient and of the condition orpathology to be modeled. In some embodiments, particularly where thepractitioner wishes to develop a surgical plan for a patient with aparticular pathology, the organ measurements can be taken directly frompatient X-ray computed tomography (“CT”) scans, magnetic resonance(“MR”) imaging, or ultrasound imaging. CT scans or MR imaging can ofcourse also be used to determine the desired size of models for moregeneral training or other applications.

Similarly, practitioners are familiar with the sizes of internalstructures and voids within each organ both in adults and in children ofdifferent ages, in both normal conditions and in pathologicalconditions. Ventricles in the brain, for example, are enlarged inpatients with normal pressure hydrocephalus. Models made for use in theinventive systems and methods can include internal structures or voids,such as ventricles, sized to represent those of pathologies a surgeonmight encounter in the course of surgery on the subject organ.

Finally, every major artery and vein serving every organ in the body hasalso been operated on in the course of surgery of the organ which thatartery or vein serves. Persons who operate on particular organs are wellaware of the typical sizes, positions and paths of each major bloodvessel providing blood to or draining blood from each organ. It isexpected that, in most organs, blood vessels do not follow a linearpath. In some embodiments, the simulated blood vessels are not linearfor more than 2 contiguous inches. In some embodiments, they are notlinear for more than 1 inch. In some embodiments, they are not linearfor more than 1 centimeter.

Making Molds

It is expected that persons of skill are generally familiar with atleast some of the various techniques for making molds and using them tocast models which have been developed over many years. Many of thesetechniques can be used in embodiments of the inventive systems andmethods.

In some embodiments, molds can be made designed using computer assisteddesign, or “CAD” software, and in particular three dimensional (3D)modeling using CAD software. A number of CAD programs useful fordesigning molds for organ models are available and include Solidworks(Dassault Systèmes SOLIDWORKS Corp., Waltham, MA), Rhino 5 (McNeel NorthAmerica, Seattle, WA), AutoCAD (Autodesk Inc., San Rafael, CA), andSketchUp (Trimble Navigation, Ltd., Sunnyvale, CA).

Molds designed by any of these programs can be printed using a 3Dprinter, such as the CubePro® (3D Systems, Rock Hill, SC), MakerBotReplicator Desktop 3D Printer, (MakerBot Industries, LLC, Brooklyn, NY),and Form 1+SLA 3D printer (Formlabs Inc., Somerville, MA).

Physiological Fluids

In some embodiments, the inventive systems and methods include fluidssimulating one or more physiological fluids that the surgeon mightencounter in the course of surgery on the subject organ. As noted above,every organ in the human body has in the aggregate been the subject ofthousands of operations over the past century and the fluids likely tobe present in both normal and in diseased organs are well known. Fluidsfor use in the inventive systems and methods will typically be water,with food coloring added to make the color appropriate for theparticular fluid being simulated: red for blood, yellow for urine, andgreen for bile. As cerebrospinal fluid (CSF) is normally clear, in someembodiments, clear water is used to represent CSF. CSF can, however, bered when there is acute bleeding into it, or yellow when old blood orchronic bleeding is present. Dyes of the appropriate colors can be usedwhere the model is intended to present surgical situations in whichconditions resulting in these colors would be present. Viscosity of thesimulated physiological fluids can be increased where desired tosimulate particular conditions by adding agents such as corn syrup orflour. Some conditions cause physiological fluids, such as urine, tobecome cloudy. If the simulated surgery is intended to be on an organhaving a condition which would result in its physiological fluid being,the cloudiness can be simulated by adding an agent, such as flour orpowdered chalk, to the simulated physiological fluid.

Hydrogels

The inventive systems and methods contemplate the use of hydrogels toform the organ models. A number of hydrogels are known in the art. Insome embodiments, the hydrogels may be a nonbiodegradable synthetichydrogel prepared from the copolymerization of various vinylatedmonomers or macromers, such as 2-hydroxyethyl methacrylate (HEMA),2-hydroxypropyl methacrylate (HPMA), acrylamide (AAm), acrylic acid(AAc),N-isopropylacrylamide (NIPAm), and methoxyl poly (ethylene glycol)(PEG) monoacrylate (mPEGMA or PEGMA), with crosslinkers, such asN,N′-methylenebis(acrylamide) (MBA), ethylene glycol diacrylate (EGDA)and PEG diacrylate (PEGDA). Poly (N-isopropylacrylamide) (PNIPAm) is athermo-sensitive polymer which can form thermosensitive hydrogels fromfree radical copolymerizing of NIPAm with crosslinkers like MBA.PEG-based hydrogels can be prepared by radiation crosslinking of PEG orfree radical polymerization of PEG macromers. The Millon patent statesthat hydrogels such as polyvinyl alcohol (PVA), poly(vinyl pyrrolidone)(PVP), poly(ethylene glycol) (PEG), poly(hydroxyethyl methacrylate)(PHEMA), polyurethanes, and polyacrylamide can be used to form surgicaltraining aids. In some embodiments, the monomers are of polyvinylalcohol.

As persons of skill appreciate, hydrogels are composed of monomers whichhave been crosslinked to form polymers. Strictly speaking, therefore, ahydrogel does not exist at the point a solution of monomers, with orwithout an initiating agent or chemical cross-linking agent, is pouredinto a mold. For ease of reference, however, it will be understood thatreferences herein to pouring a hydrogel into a mold refers to pouring amixture comprising monomers of the desired hydrogel, along with anyinitiating agents, catalysts, or other chemicals which may be needed toinitiate or facilitate cross-linking the monomers into a hydrogel of thedesired stiffness. Forming hydrogels using different monomers anddifferent cross-polymerization techniques are well known in the art,including freeze/thaw cycling, radiation, ultra-violet illumination, andchemical catalysts (reviewed in, e.g., Ahmed, E., “Hydrogel:Preparation, characterization, and applications: A review,” J. Adv.Res., 6(2):105-121 (2015)). It is assumed that persons of skill arefamiliar with these teachings. In some preferred embodiments, themonomers are polymerized by freeze/thaw cycling.

Coloring Organ Models

If desired, coloring agents can be added to the hydrogel so that themodel organ has a color more closely mimicking the color and appearanceof the subject organ. For example, food colors can be added to thehydrogel monomers prior to casting of the model. In other embodiments,1% colored, powdered chalk can be added. Higher percentages of coloredchalk can be used to create enhanced images or calcified appearance onimaging. Indocyanine green or other near-infrared dyes can be placedinto areas representing tumors to allow the practitioner to visualizethe area in which resection should be performed using intra-operativedevices, such as the SPY ELITE® system (Novodaq Technologies Inc.,Bonita Springs, FL). In these embodiments, the tumor model is typicallycreated first and registered to the intended position within the organmold. The organ is then modeled by flowing hydrogel monomer mix into themold around the organ and crosslinked.

Crosslinking and Polymerizing the Hydrogel

Once a hydrogel is poured, it is crosslinked, typically to a degree ofstiffness approximating that of the subject organ. A variety of meansare known in the art, including radiation, chemical cross-linking, andfreeze/thawing. Freeze/thawing, in particular, allows for gradedpolymerization of the hydrogel which progressively harden the hydrogel,leading to the desired stiffness and associated mechanical properties.

The parameters of the hydrogel and polymerization method can be adjustedso that the “feel” of the resulting models closely replicates the feelof the subject organ. For example, one can adjust the concentration ofthe monomers, typically up to 20% by weight (as the name “hydrogel”implies, the remaining percentage is water), as well as the number offreeze/thaw cycles, from one up to ten, with models of softer organssuch as the brain being constructed using a lower concentration ofmonomers and a lower number of freeze/thaw cycle and firmer organs beingmade using a higher concentration of hydrogel monomers and a highernumber of freeze/thaw cycles. In studies underlying the presentdisclosure, one of the inventors, an experienced urologist, found thatstarting with a PVA concentration of 10% which was then subjected tofour freeze/thaw cycles subjectively felt like a kidney. It is expectedthat surgeons are typically familiar with the feel of the organs onwhich they operate and can feel organ models made with varyingconcentrations of hydrogel and varying numbers of freeze/thaw cycles orother crosslinking techniques and readily determine whether anyparticular model has the desired subjective feel of the subject organ.

In some respects, the brain presents a special case for modeling. Aspersons of skill will appreciate, in vivo, the ventricles of the brainare filled with fluid. As the brain has a “stiffness” somewhat likegelatin, in some embodiments, in which models of the brain are not goingto have the modeled ventricles filled with fluid, the hydrogel can becrosslinked by an extra freeze/thaw cycle over that which wouldotherwise be used so that the model has a degree of stiffness sufficientto keep the ventricles open and preserve the spatial relationships ofthe ventricles to the exterior surface of the model brain. Conversely,when the ventricles of the model are to be filled with fluid (typicallywater) before the simulated surgery, and particularly where the fluid isto be placed under pressure to simulate hydrocephalus (by, for example,hanging a bag of fluid outside the model, which bag is connected by atube to one or more model ventricles in the brain model), the model ofthe brain is preferably of the normal stiffness of the brain, so thatthe person performing the simulated surgery will obtain a bettersimulation of the surgical experience.

In addition to providing models for surgery on the organs themselves, insome embodiments, the inventive systems and methods combine model organswith simulations of other tissues or organs to simulate surgery onportions of the body, such as a torso or an abdomen. In this regard,models or one or more organs may be disposed in a larger hydrogelconstruct simulating, for example, an abdomen, with hydrogel modelingabdominal muscles and fat. Studies underlying the present disclosurefound, for example, that fat could be simulated using PVA monomers at aconcentration of 2.5% subjected to 2 freeze/thaws, while muscle could besimulated using PVA monomers at a concentration of 10% subjected to 3freeze/thaws.

Persons of skill will also appreciate that there are additionalvariables that affect the stiffness of the model, including the volumeof the organ, as the rate at which models freeze and thaw affectsstiffness. A larger model will freeze and thaw more slowly and will bestiffer after one cycle than will a model of a smaller organ. Thus, if amodel of a kidney is being made on its own at a concentration of 10%, itwill reach appropriate stiffness after 4 freeze/thaw cycles, but ifbeing made as part of an abdomen or torso, it will typically besubjected to one freeze/thaw cycle by itself, and then be placed intothe larger model of the abdomen or torso and subjected to a secondfreeze/thaw cycle. Since the model will freeze and thaw more slowlywithin the model of the abdomen or torso than it does on its own, themodel kidney will now have the desired stiffness after the second cycle.

While there may be differences in the particular combinations of monomerconcentrations and number of freeze/thaw cycles or other crosslinkingmethods that are best for creating the stiffness desired to model anyparticular organ, testing combinations is usual in modeling. It is wellwithin the skill of one in the art to determine the combination ofmonomer concentrations and freeze/thaw cycles or other polymerizationtechniques to achieve the stiffness of any particular organ beingmodeled.

Wires, Removable Elements, and Inner Components

As noted, a variety of elements can be placed in the mold of an organ orportion thereof to allow representation of internal features of anorgan, including voids to create the path of blood vessels in the organ.Unfortunately for those creating models, most internal structures andvoids in organs are not linear. Accordingly, accurate representation ofthese structures and voids requires non-linear elements, and these inturn can be problematic to remove once hydrogel has been crosslinkedaround the element. The inventive systems, models and methods providemodels with surprisingly better representation of non-linear structuresand voids than has been possible with previous systems.

In some embodiments, the elements used to represent the internalstructures or voids are pliant wires. Pliant wires offer a degree ofrigidity useful in bending the wires into positions in the moldregistered to where the blood vessels appear in the organ, while thepliancy is useful in gently withdrawing the wires after the hydrogelmonomers have been introduced into the mold, typically by pouring orinjecting, and undergone crosslinking to a first desired stiffness. Ifnecessary, the element, such as the pliant wire, can be suspended in themold by, for example, suturing it to the side of the mold or securing itto the outside of the mold with, for example, a fine wire.

It will be appreciated that, as the diameter of the blood vessel beingmodeled becomes larger, wires of the corresponding diameter, even thoughpliant, may be too firm to be withdrawn without unacceptable tearing ofthe hydrogel. In such cases, an element pliant at the desired diameter,such as a soft plastic tube or a shoestring can be used. If the pliantelement is not sufficiently rigid by itself to maintain the desiredshape and position within the mold without support, a thin pliant wirecan be threaded through the pliant element to increase its rigiditywithout losing the desired pliancy.

In some embodiments, more detail or structure may be desired than can berepresented by a pliable element, such as a wire or tube. Such innerfeatures of the model organ can be created by creating the feature inparts, using half negative molds with positive inserts that permit thefeature to be “shelled.” After introducing hydrogel monomer mixture intothe mold, the mixture is subjected to an initial crosslinking, forexample, by subjecting the mold to a first freeze. The positive insertsare removed leaving a raw surface, and the two “negative” molds are thenattached to form the intact hollow feature. For example, if thecrosslinking is by freeze/thawing the hydrogels, the casts from each oftwo half molds can be “glued” together by placing more hydrogel at theseam of the join, mating the two casts, and then subjecting the twomolds to a freeze. Upon the subsequent thaw, the hydrogels crosslink,fusing the casts together.

Joining Subparts or Halves to Form Models of Organs

As noted above, in some embodiments, the subject organ is convenientlymodeled by using molds of parts of the subject organ (as noted earlier,there can be two molds, in the case of bi valve molding, or three ormore in the case of piece casting. For convenience of reference in thissection, the term “subpart” refers to a model cast in a mold of a partof the subject organ). As also noted, one or more of these molds willhave disposed within it elements simulating internal structures, such asblood vessels, internal voids, or pathology such as an exophytic orendophytic tumor. Hydrogel is introduced into the respective molds toflow around any elements disposed within the mold and fill the mold. Thehydrogel is then crosslinked to a desired degree of stiffness. In someembodiments, the crosslinking is by subjecting the hydrogel to at leastone freeze-thaw cycle. Cross linking by freeze-thaw cycles is useful, asit provides a convenient way to bring the hydrogel to any desired degreeof stiffness within the range of the hydrogel.

As described earlier, in some embodiments, some or all of these elementsare intended to be in place in the model of the intact organ. In otherembodiments, however, some elements, such as the wires 105 and 106 shownin FIG. 1 , are intended to be removed once the hydrogel has reached atleast a first degree of stiffness, but before the subparts cast in themolds are joined and attached. If the hydrogel is being crosslinked bysubjecting the hydrogel to freeze-thaw cycles, elements to be removedare typically removed after the first freeze-thaw cycle of thecomponent. Where wires are used, they are removed before final assemblyof the model (arranging the components in their anatomical positions andattaching), usually after the component has undergone at least its ownfirst round of crosslinking, such as undergoing a freeze/thaw cycle.Wires are typically kept in subparts until the largest part of thecomponent in which the subpart appears (such as the calyx in a kidney ora tumor in a uterus) is completed.

Once any elements that are to be removed have been removed, the modelsin the separate molds are mated and attached. In some embodiments, theattachment is by suturing the models together. In some embodiments, theattachment is by gluing the models together. In some embodiments, theattachment is by adding a layer of hydrogel to the surfaces to be matedand crosslinking the hydrogel. In some embodiments, the crosslinking isby subjecting the model to at least one freeze-thaw cycle.

Mapping Internal Components of the Model

As noted, the models used in the inventive systems and methods can havedisposed within them simulated blood vessels, internal voids, such asbrain ventricles or kidney calyxes, pathology such as tumors, and otherfeatures. The position and space occupied by the various structures andfeatures within each organ are well known in the art. The terms“registering” or “mapping” simulations of such structures with referenceto models of the organs in which they appear denotes that the simulatedfeatures or structures are positioned in a mold of a part of a subjectorgan so that when a model of the subject organ is made using thecasting from that mold, the simulated feature or structure will appearin the same position and have the same size and shape as the feature orstructure it is intended to simulate. As an example, an artery supplyingblood to a particular organ typically enters that organ at a particularposition, and in the case of an artery, branches into arterioles andfinally capillaries along a defined path. Further, the artery servingeach organ has a typical shape and a size which depends on factors suchas the size and age of the individual and in some cases pathology. Theseshapes and sizes are after a century of operations and autopsies wellknown to practitioners. If desired, the artery (or other structure orinternal void in the organ of interest) can be imaged by MRI, CT, orother imaging modalities and the size, shape and position of the organand internal structures measured on the images or directly entered ormapped into a software program for modeling the organ or structure. Asused herein, the phrase “size, shape and position are mapped to acorresponding internal structure or void having a like, shape andposition within said anatomical organ” refers to an internal structureor internal void in a model of an anatomical organ that is of the samesize and shape, and traversing the same path over the length of thatinternal structure or void as does the internal structure or void in theanatomical organ being modeled. As noted, the anatomical organ beingmodeled can be that of a particular individual, which can be of one witha common pathology or of an unusual pathology or a pathology on whichthe practitioner wishes to practice (except for removing organs fortransplant, surgery is not usually performed on organs or on patientsthat do not have pathology).

The element used to simulate the internal structure or feature may besufficiently rigid to remain in the desired position within the mold ofthe organ during the pouring and crosslinking of the hydrogel to createthe model of the organ with the internal structure in place. In manyembodiments, however, it will be necessary to secure the model of theinternal structure or feature in place during at least the initialpouring and crosslinking of the polymer that will form the model organby, for example, using sutures, thin wires, or fishing line to suspendthe model of the internal structure within the mold for the model organ(for convenience, when used in this fashion, a suture, wire, fishingline or other material may be referred to as a “suspension cable”).

Use of suspension cables facilitates mapping of the internal structureor feature to a location within the model organ corresponding to theposition of the internal structure in the anatomical organ (or, in thecase of, for example, a tumor which is not normally present in theanatomical organ, in the desired position within the organ model). Insome embodiments, the model of the internal structure is created, and asuspension cable then inserted into and through the model of theinternal structure at a position chosen so that, once the cable isattached to the mold of the model organ, the model of the internalstructure will be located in the correct position within the model organonce the organ mold is cast within the mold. In some embodiments, themodel of the internal structure is created (cast) with a spanningsuspension cable within the mold of the internal structure, whicheffectively mounts the resulting model of the internal structure on thecable when the mold is cast. In these embodiments, once cast, the cableis positioned within the model of the internal structure and hasportions extending beyond the model of lengths such that when the cableis fitted into the mold of the organ, and the mold of the organ is cast,the model of the internal structure will be suspended within theresulting model of the organ at a position mapped to the location of thecorresponding internal structure in the anatomic organ. This isconveniently accomplished by having the model of the internal structurelocated at a specific distance along the length of the cable andspanning a specific portion of the internal structure. For example,depending on where the model of the internal structure is to bepositioned within the mold of the organ, the cable may run through thecenter of the model of the internal structure or may run through oneside or the other. To suspend the internal structure in some positions,it may be convenient to use more than one cable.

Once the internal structure is created (with or without one or moreembedded suspension cables), it is placed in the mold of the anatomicorgan so that its location is mapped to the desired spot. This can beachieved by having features in the mold that accept the internalstructure, the suspension cable (if one or more is present), or both.For example, if the designer wishes to provide a model organ having atumor and a blood vessel adjacent to each other in the anterior face ofthe superior pole of the kidney, both of these inner features can bemounted on a single suspension cable which traverses the mold of thekidney at a specific angle with a specific trajectory such that bothinner features lay where they are supposed to be. Alternatively, thefeatures can be on separate cables each with specific angles andspecific trajectories to accomplish the same result. Holes can befashioned in the kidney mold so that the cable or cables can crossthrough the superior pole of the model kidney and placed off center suchthat the holes position the internal structures in the anterior face ofthe model. Persons of skill will appreciate that the specific angles andspecific trajectories chosen to accomplish these results will varyaccording to the specific organ being modeled and the specific internalstructures to be modeled, but are easily accomplished.

After the first crosslinking, any suspension cable or cables used arepreferably removed. We have found that suspension cables such aspolypropylene sutures leave holes fine enough that the holes seal overand leave both the model of the internal structure and of the organmodel water-tight. Without wishing to be bound by theory, it is surmisedthat there are expansive forces on the hydrogel “tissue” that result inclosure of the small holes resulting from removal of the suspensioncables.

In some embodiments, the model includes pathologies, such as tumors,whose position within a particular organ are not defined by theirposition in a normal organ, as by definition a normal organ would notcontain the pathology. In such instances, the pathology may beregistered by where tumors are most commonly found in the subject organ,or may be disposed at positions selected to present a surgical problemof a selected degree of difficulty or complexity.

Some aspects of mapping internal features to desired positions withinthe organ model may be better understood by reference to FIG. 5 . FIG. 5is a diagram showing a mold 501 for an organ model. Suspension cable 502runs through the center of model tumor 503 and is registered withinorgan mold 501 through holes 504 and 505 (for visibility, holes 504 and505 are shown as larger than they would be in the model). Tumor 503 isslightly closer to hole 504 so that it is off the midline of the organmodel 501. A simulated blood vessel, 506, is mounted on suspensioncables 507 and 508. (The points at which simulated blood vessel 506enters and exits the organ model are not shown in this sectional view.)In this example, suspension cables 507 and 508 do not pass throughsimulated blood vessel 506, which is instead tied to cables 507 and 508by a length of fine thread (not shown). Suspension cables 507 and 508are registered through holes 509 and 510 and holes 511 and 512,respectively (holes 509-512 are shown as larger than they would be inthe model so that they can be seen in the figure). This arrangementallows the inner features, such as the tumor and the vessel, to bepositioned at what will become selected locations within the model. Thepolymer mix that will form the organ model is then poured around thetumor 503, vessel 506, and cables 502, 507, and 508, and polymerized,such as by subjecting the polymer mix to one or more freeze thaw cycles,until the model organ is at a degree of firmness desired by thepractitioner. Cables 502, 507 and 508 are then removed (by simplypulling them from one end or, if desired and if the cables are made ofdissolvable filaments, by dissolving them). The removal or dissolving ofcables 502, 507 and 508 leaves the internal structures mapped to thedesired positions within the model organ. For convenience ofillustration, cables 502, 507 and 508 are shown as straight lines.Persons of skill will recognize, however, that flexible wires (ordissolvable filaments) can be used to create curved paths for the cablesif desired to facilitate registration of the internal features.

It is understood that the examples and embodiments described herein arefor illustrative purposes only and that various modifications or changesin light thereof will be suggested to persons skilled in the art and areto be included within the spirit and purview of this application andscope of the appended claims. All publications, patents, and patentapplications cited herein are hereby incorporated by reference in theirentirety for all purposes.

The invention claimed is:
 1. A system for simulating surgery on ananatomical organ, said system comprising: a) a mold for making a modelin the shape of an anatomical organ, said mold having first and secondopposing mold walls defining an internal mold cavity therebetween in theshape of said model, said internal mold cavity configured to receive amold material therein to form said model, said mold including first andsecond holes formed through first and second opposing mold walls; b) aunitary suspension cable having first and second opposite ends removablythreaded through and releasably secured at said first and second holes,respectively, with the portion of said suspension cable located betweensaid first and second ends fully traversing and suspended within saidinternal mold cavity between said first and second holes; and c) one ormore elements removably mounted at a predetermined location along saidportion of said suspension cable within said internal mold cavity,wherein said one or more elements when mounted within said internal moldcavity forms one or more respective internal structures or internalvoids in the molded model upon release and removal of said unitarysuspension cable from said first and second holes.
 2. The system ofclaim 1, further comprising the model in the shape of said anatomicalorgan made from said mold, said model composed of a crosslinked hydrogelsimulating a tactile property of said anatomical organ, and havingdisposed in said internal mold cavity said one or more elements, said atleast one or more respective internal structures or internal voidshaving a size, shape and position within said model mapped to one ormore respective internal structures or voids having substantially thesame shape and position within said anatomical organ.
 3. The system ofclaim 2, further wherein said model comprises a plurality of saidinternal structures or internal voids.
 4. The system of claim 3, furtherwherein said at least one internal structure or internal void of saidmodel contains a simulated physiological fluid of said anatomical organ.5. The system of claim 3, further wherein at least one said internalvoid in said model is a channel in said material simulating an artery orvein of said anatomical organ.
 6. The system of claim 5, further whereinsaid simulated artery or vein contains simulated blood.
 7. The system ofclaim 2, further comprising at least one simulated tumor disposed in oron said model of said anatomical organ.
 8. The system of claim 7,further wherein said tumor is at a position corresponding to a positionat which tumors occur in said anatomical organ.
 9. The system of claim7, further comprising a plurality of simulated tumors at positionscorresponding to positions at which tumors occur in said anatomicalorgan.
 10. The system of claim 2, further wherein said internalstructure or internal void of said model is not linear within said modelfor more than two contiguous inches.
 11. The system of claim 1 whereinat least one of said elements is a structure located within said modelfollowing removal of said unitary suspension cable.